1. Field of the Invention
The present invention relates to a method of evaluating lung cancer, a lung cancer-evaluating apparatus, a lung cancer-evaluating method, a lung cancer-evaluating system, a lung cancer-evaluating program and recording medium, which utilize the concentration of amino acids in blood (plasma).
2. Description of the Related Art
The number of deaths from lung cancer in Japan in 2003 is 41634 males and 15086 females, which account for 18.3% of deaths from all cancers, and the number of deaths from lung cancer ranks first in males. The number of deaths from lung cancer ranks third in females, but is increasing year by year and is currently presumed to rank first in the near future.
At present, lung cancer is a hardly curable cancer, and more than half of cases when detected have already been advanced and are inoperable. On the other hand, the five year survival rate in early lung cancer (stage I to II) is 50% or more, and particularly the five year survival rate in lung cancer at stage IA (tumor of 3 cm or less in size with no lymph node metastasis and with no infiltration into surrounding organs) is about 90%, and early detection is important for cure of lung cancer.
Diagnosis of lung cancer includes diagnosis by imaging with X-ray picture, CT (computer tomography), MRI (magnetic resonance imaging), PET (positron emission computerized-tomography) and the like, sputum cytodiagnosis, lung biopsy with a bronchoscope, lung biopsy with a percutaneous needle, and lung biopsy by exploratory thoracotomy or with a thoracoscope.
However, diagnosis by imaging does not serve as definitive diagnosis. In chest X-ray examination (indirect roentgenography) for example, the positive-finding rate is 20% but the specificity is 0.1%, and almost all of persons with positive-finding are false-positive. The detection sensitivity is low, and some examination results according to Ministry of Health, Labour and Welfare, Japan, showed that in the case of indirect roentgenographic examination, about 80% of patients with onset of lung cancer were overlooked in chest X-ray examination. There is a concern that these methods are poor in both detection sensitivity and detection specificity, particularly in early lung cancer. In chest X-ray examination, there is also a problem of exposure of subjects to radiation. Carrying out the mass screening by CT, MRI, PET and the like, on the other hand, is problematic from the viewpoint of facilities and costs.
Patients who can be definitely diagnosed in sputum cytodiagnosis are only 20 to 30%. Lung biopsy using a bronchoscope, a percutaneous needle, exploratory thoracotomy or a thoracoscope serves as definitive diagnosis but is a highly invasive examination, and thus lung biopsy of all patients suspected of having lung cancer in diagnostic imaging is not practical. Such invasive diagnosis is accompanied by a burden such as suffering in patients, and there can also be a risk such as bleeding upon examination. For reducing a physical burden on patients and for cost-benefit performance, it is desired that subjects with high possibility of onset of lung cancer are selected by a less-invasive method and then diagnosed definitively as those with lung cancer by lung biopsy, followed by treatment.
On the other hand, the amino acid concentration in blood is known to change due to the onset of cancer. For example, Cynober (“Cynober, L. ed., Metabolic and therapeutic aspects of amino acids in clinical nutrition. 2nd ed., CRC Press.”) has reported that for example, the amount of glutamine consumed mainly as an oxidation energy source, the amount of arginine consumed as a precursor of nitrogen oxide and polyamine, and the amount of methionine consumed by activation of the ability of cancer cells to incorporate methionine are increased respectively in cancer cells. Proenza (“Proenza, A. M., J. Oliver, A. Palou and P. Roca, Breast and lung cancer are associated with a decrease in blood cell amino acid content. J Nutr Biochem, 2003. 14(3): p. 133-8.”) and Cascino (“Cascino, A., M. Muscaritoli, C. Cangiano, L. Conversano, A. Laviano, S. Ariemma, M. M. Meguid and F. Rossi Fanelli, Plasma amino acid imbalance in patients with lung and breast cancer. Anticancer Res, 1995. 15(2): p. 507-10.”) have reported that the amino acid composition in plasma in lung cancer patients is different from that of healthy individuals. Rodriguez (“Rodriguez, P. C., C. P. Hernandez, D. Quiceno, S. M. Dubinett, J. Zabaleta, J. B. Ochoa, J. Gilbert and A. C. Ochoa, Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med, 2005. 202(7): p. 931-9.”) has reported that an increase in the gene expression and enzyme activity of arginase I is recognized in bone marrow cells contacted with cancer cells, and as a result, the concentration of arginine in plasma is reduced.
However, there is a problem that the development of techniques of diagnosing the presence or absence of onset of lung cancer with a plurality of amino acids as variables is not conducted from the viewpoint of time and cost and is not practically used.